This proposed research represents a continuation of work on the biochemistry and biology of human Cl, the first complement component and its substrates. Cl is activated by a variety of biological materials and initiates a cascade reaction beginning with the proteolytic cleavage of its natural substrates C4 and C2. Cleavage of C4 and C2 lead to convertase formation with the ability to cleave C3. Generation of capillary permeability, chemotactic, opsonic and lytic activities results and these reactions appear to play fundamental roles in acute and probably in chronic inflammation, irrespective of the method by which the cascade process was initiated. This project has placed an emphasis on isolating and characterizing naturally occurring inhibitors of the early classical components. Current research efforts have been devoted to purifying and characterizing the most recently discovered complement inhibitor - Clq inactivator (ClqINA). We have identified this inactivator as a chondroitin 4-sulfate proteoglycan and research is underway to more specifically define its biochemistry and to assess its role in modulating Clq activity in vivo.